Statine analogs

All statine analogs have the (3S,4S) configuration. ° dSta, 4-amino-6-methylheptanoic acid. 

An unusual inhibitor of aspartyl proteases that may be another type of collected-substrate inhibitor, has been discovered as a result of systematic modification of statine. Because x-ray data (Figure 2) suggested that the pro-R hydrogen in statine could be replaced by a methyl group without encountering steric interactions with the enzyme, we synthesized new statine analogs in which the C-3 proton was replaced by a methyl group. 

Much less is known about aldol additions to chiral aldehydes that have heteroatoms other than oxygen at the a-stereocenter. In connection with a synthesis of statine analogs, a-amino aldehyde (176) was allowed to react with ethyl lithioacetate to obtain (177) and (178) in a ratio of 60 40 (equation 114). 

Figure 2.16 Combinatorial hybrid biosynthesis of statin analogs.

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